US8765196B2 - Method for separating and purifying Ginkgolide C from root bark of ginkgo - Google Patents
Method for separating and purifying Ginkgolide C from root bark of ginkgo Download PDFInfo
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- US8765196B2 US8765196B2 US14/006,474 US201214006474A US8765196B2 US 8765196 B2 US8765196 B2 US 8765196B2 US 201214006474 A US201214006474 A US 201214006474A US 8765196 B2 US8765196 B2 US 8765196B2
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- 0 [1*]C12C(C)C(=O)OC1([H])[C@@H]([2*])C13C24OC2([H])OC(=O)[C@H](O)[C@@]21[C@H](C(C)(C)C)C([3*])[C@]3([H])OC4=O Chemical compound [1*]C12C(C)C(=O)OC1([H])[C@@H]([2*])C13C24OC2([H])OC(=O)[C@H](O)[C@@]21[C@H](C(C)(C)C)C([3*])[C@]3([H])OC4=O 0.000 description 2
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
Definitions
- the invention relates to a ginkgolide, and specifically to a method for separating and purifying Ginkgolide C in high purity from the root bark of ginkgo.
- Ginkgolide compounds belong to terpenoids and are also known as ginkgo terpene lactones which are composed of sesquiterpene lactones and diterpene lactones. Moreover, they are an important active ingredient in leaves of ginkgo.
- Ginkgolide C is a diterpene lactone compound, which was firstly separated from leaves of ginkgo by S. Furukawa in 1932, and was further separated and identified the chemical structure thereof by K. Nakanish, M. Maruyama and K. Okabe, et al. in 1967.
- Ginkgolide compounds have a molecular skeleton consisting of 20 carbon atoms and having 6 five-membered rings: 2 five-membered carbocyclic rings, 3 five-membered lactone rings, and 1 tetrahydrofuran ring, in which 2 five-membered carbocyclic rings are linked together in the form of a spiro ring, and the other rings are fused together, so as to form the following particular rigid cage stereochemical structure.
- All the ginkgolides have a potent antagonist of platelet activating factor, and are a particular active ingredient in each part of ginkgo plant.
- the content of the ginkgolides is highest in the root bark of ginkgo, which is about three times of that in ginkgo leaves.
- the ginkgolide compounds are bitter white crystals with the melting point of about 300° C. Because a hydroxy group/hydroxy groups and several oxygen-containing ester groups are present in molecule, the ginkgolide compounds have higher polarity than common sesquiterpene and diterpene compounds, and are soluble in organic solvents such as ethanol, acetone, butanone, ethyl acetate, dimethyl sulfoxide and the like.
- the ginkgolide compounds are very stable against concentrated acids and strong oxidants. After a ginkgolide compound is dissolved in concentrated nitric acid and then evaporated to dryness, the lactone thereof would not be destroyed.
- the ginkgolide compound comprises several lactone structures in molecule.
- the ginkgolide compound can be reacted with a base to produce a salt which is soluble in water. If the resulting salt is acidified with an acid, it will convert to the initial lactone which is insoluble in water but soluble in an organic solvent. Therefore, this property can be used for the extraction and separation of ginkgolides.
- the ginkgolides from leaves of ginkgo are generally obtained by extracted, separated on columns, and then further separated by a high performance liquid preparative chromatography to achieve a purity of 95%. That is, macroporous adsorptive resin only contributes to the removal of impurities and the enrichment in the process, but does not actually contribute to the purification.
- An object of the invention is to provide a method for separating and purifying Ginkgolide C from the root bark of ginkgo, which is a simple and convenient method for separating and purifying Ginkgolide C and suitable for industrial production.
- the method can overcome the drawbacks in the prior art, such as the complex process flow, the low yield, the poor selectivity of separation and purification, and the high cost of industrial production as well as the final product not suitable for direct use as a pharmaceutical raw material.
- the inventor provides a method carried out by the following steps:
- the extract is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C. until no taste of ethanol is present. At this moment, the volume of the concentrate is about 1 ⁇ 3 of the initial extract volume.
- the type of the resin used in the column chromatography is DM130, D101 or AB-8.
- the pure water for removing impurities is neutral, and the amount of the pure water is 2 folds column volume; the amount of 80% to 90% by weight of ethanol for eluting is 3-4 folds column volume.
- the eluate is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C.
- the solution is refrigerated at a temperature of 2° C. to 6° C. for 12 hours.
- the supernatant solution is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C.
- the crystal is recrystallized three times.
- step (1) during the extraction process of step (1), the use of 50% by weight of ethanol for extraction is preferable to water because of the following reasons: first of all, the use of 50% by weight of ethanol for extraction results in a higher extraction ratio of lactones than water; secondly, the extract of water contains more proteins and polysaccharide substances which is not suitable for being loaded on column, while the use of the aqueous alcohol solution can reduce the proteins and polysaccharide substances in the extract to reduce the viscosity of the solution, which is suitable for being loaded on column.
- the inventor further points out that: in the step (8), the crude crystal is dissolved in 95% by weight of ethanol to form a supersaturated solution, and then undergoes fractional crystallization according to the polarity of the lactones to remove Ginkgolide A and Ginkgolide B, namely, Ginkgolide B is firstly crystallized out and the mother liquor is suitably concentrated to crystallize Ginkgolide A, thus the mother liquor mainly comprises Ginkgolide C and little Ginkgolide A; the mother liquor is further concentrated to obtain a crystal of Ginkgolide C with the content of more than 80%, in which less than 5% of Ginkgolide A is present.
- the method of the invention can obtain a high-purity Ginkgolide C with a purity of more than 97% by the separation and purification from the root bark of ginkgo. Moreover, the method of the invention has advantages such as the simple process flow, the good product quality and the low cost of industrial production and so on.
- the extract was concentrated under vacuum to remove ethanol, and the concentration was conducted under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C. until no taste of ethanol was present, and the volume of the concentrate was about 200 L;
- the concentrate was separated by macroporous resin column chromatography, the type of the resin was AB-8, the amount of the resin was 100 kg, and the diameter-height ratio of the column was 1:8 or 1:10;
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicines Containing Plant Substances (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Disclosed is a method for separating and purifying Ginkgolide C from root bark of ginkgo. The method comprises: (1) extracting the root bark of ginkgo with ethanol; (2) concentrating the resulting extract under vacuum to remove ethanol; (3) separating the concentrate by macroporous resin column chromatography; (4) after the concentrate being loaded on the column, washing the column with pure water to remove impurities, and then eluting the column with an ethanol solution; (5) concentrating the eluate under vacuum to dryness to obtain a yellow crude extract; (6) heating the crude extract in water to boiling to form a solution, and then refrigerating the solution; (7) concentrating the supernatant solution and filtering under vacuum to obtain a mixed crude crystal of ginkgolides; (8) dissolving the crude crystal in ethanol to form a supersaturated solution, refrigerating and crystallizing the solution to remove Ginkgolides A and B; (9) concentrating and recrystallizing the mother liquor to obtain a crystal of Ginkgolide C; and (10) recrystallizing the crystal with ethanol several times to obtain a high-purity crystal of Ginkgolide C.
Description
This application is a national stage entry of PCT Application No. PCT/CN2012/071584, filed Feb. 24, 2012, which claims priority to Chinese Application No. 201110067186.9, filed Mar. 21, 2011. Each of the aforementioned applications are incorporated by reference herein.
The invention relates to a ginkgolide, and specifically to a method for separating and purifying Ginkgolide C in high purity from the root bark of ginkgo.
Ginkgolide compounds belong to terpenoids and are also known as ginkgo terpene lactones which are composed of sesquiterpene lactones and diterpene lactones. Moreover, they are an important active ingredient in leaves of ginkgo.
Ginkgolide C is a diterpene lactone compound, which was firstly separated from leaves of ginkgo by S. Furukawa in 1932, and was further separated and identified the chemical structure thereof by K. Nakanish, M. Maruyama and K. Okabe, et al. in 1967. Ginkgolide compounds have a molecular skeleton consisting of 20 carbon atoms and having 6 five-membered rings: 2 five-membered carbocyclic rings, 3 five-membered lactone rings, and 1 tetrahydrofuran ring, in which 2 five-membered carbocyclic rings are linked together in the form of a spiro ring, and the other rings are fused together, so as to form the following particular rigid cage stereochemical structure.
All the ginkgolides have a potent antagonist of platelet activating factor, and are a particular active ingredient in each part of ginkgo plant. The content of the ginkgolides is highest in the root bark of ginkgo, which is about three times of that in ginkgo leaves. The ginkgolide compounds are bitter white crystals with the melting point of about 300° C. Because a hydroxy group/hydroxy groups and several oxygen-containing ester groups are present in molecule, the ginkgolide compounds have higher polarity than common sesquiterpene and diterpene compounds, and are soluble in organic solvents such as ethanol, acetone, butanone, ethyl acetate, dimethyl sulfoxide and the like.
The ginkgolide compounds are very stable against concentrated acids and strong oxidants. After a ginkgolide compound is dissolved in concentrated nitric acid and then evaporated to dryness, the lactone thereof would not be destroyed. The ginkgolide compound comprises several lactone structures in molecule. The ginkgolide compound can be reacted with a base to produce a salt which is soluble in water. If the resulting salt is acidified with an acid, it will convert to the initial lactone which is insoluble in water but soluble in an organic solvent. Therefore, this property can be used for the extraction and separation of ginkgolides.
Currently, many studies are focused on the separation and purification of the ginkgolides from leaves of ginkgo, but there are few reports regarding the separation and purification of ginkgolides from root bark of ginkgo. The ginkgolides from leaves of ginkgo are generally obtained by extracted, separated on columns, and then further separated by a high performance liquid preparative chromatography to achieve a purity of 95%. That is, macroporous adsorptive resin only contributes to the removal of impurities and the enrichment in the process, but does not actually contribute to the purification. Moreover, the use of C18 column increases the process steps and production cost, so that the entire process for separation and purification is relatively complex, the yield is low, the cost is expensive, and a mass production is difficult to carry out. Only one patent application with application No. 201010294667.9, titled “A PROCESS FOR EXTRACTING GINKOGLIDES A AND C FROM ROOT BARK OF GINKGO”, relates to the separation and purification of ginkgolides from the root bark of ginkgo. However, the technical solution of the patent application can only obtain a mixture of Ginkgolides A and C, and cannot directly offer a high-purity Ginkgolide C.
An object of the invention is to provide a method for separating and purifying Ginkgolide C from the root bark of ginkgo, which is a simple and convenient method for separating and purifying Ginkgolide C and suitable for industrial production. The method can overcome the drawbacks in the prior art, such as the complex process flow, the low yield, the poor selectivity of separation and purification, and the high cost of industrial production as well as the final product not suitable for direct use as a pharmaceutical raw material.
The inventor provides a method carried out by the following steps:
(1) extracting the root bark of ginkgo as a raw material with 50% by weight of ethanol;
(2) concentrating the resulting extract under vacuum to remove ethanol;
(3) separating the concentrate by macroporous resin column chromatography;
(4) after the concentrate being loaded on the column, washing the column with 2 folds column volume of pure water to remove impurities, and then eluting the column with 80% to 95% by weight of an ethanol solution;
(5) concentrating the eluate under vacuum to dryness to obtain a yellow crude extract;
(6) heating the crude extract in water to boiling to form a solution, and then refrigerating the solution;
(7) concentrating the supernatant solution to ⅕ volume of the initial volume to produce a large number of lactone particles, and then filtering under vacuum with filter paper to obtain a white mixed crude crystal of ginkgolides;
(8) dissolving the crude crystal in 95% by weight of ethanol to form a supersaturated solution, refrigerating and crystallizing the solution to remove Ginkgolides A and B;
(9) concentrating and recrystallizing the mother liquor to obtain a crystal of Ginkgolide C with a content of more than 80%; and
(10) recrystallizing the crystal with ethanol several times to obtain a high-purity crystal of Ginkgolide C.
In the step (1), 50% by weight of ethanol is added at a material-liquid ratio of 1:8, and the resulting mixture is heated to 70° C. to extract for 2 hours.
In the step (2), the extract is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C. until no taste of ethanol is present. At this moment, the volume of the concentrate is about ⅓ of the initial extract volume.
In the step (3), the type of the resin used in the column chromatography is DM130, D101 or AB-8.
In the step (4), the pure water for removing impurities is neutral, and the amount of the pure water is 2 folds column volume; the amount of 80% to 90% by weight of ethanol for eluting is 3-4 folds column volume.
In the step (5), the eluate is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C.
In the step (6), the solution is refrigerated at a temperature of 2° C. to 6° C. for 12 hours.
In the step (7), the supernatant solution is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C.
In the step (10), the crystal is recrystallized three times.
The inventor points out that: during the extraction process of step (1), the use of 50% by weight of ethanol for extraction is preferable to water because of the following reasons: first of all, the use of 50% by weight of ethanol for extraction results in a higher extraction ratio of lactones than water; secondly, the extract of water contains more proteins and polysaccharide substances which is not suitable for being loaded on column, while the use of the aqueous alcohol solution can reduce the proteins and polysaccharide substances in the extract to reduce the viscosity of the solution, which is suitable for being loaded on column.
The inventor further points out that: in the step (8), the crude crystal is dissolved in 95% by weight of ethanol to form a supersaturated solution, and then undergoes fractional crystallization according to the polarity of the lactones to remove Ginkgolide A and Ginkgolide B, namely, Ginkgolide B is firstly crystallized out and the mother liquor is suitably concentrated to crystallize Ginkgolide A, thus the mother liquor mainly comprises Ginkgolide C and little Ginkgolide A; the mother liquor is further concentrated to obtain a crystal of Ginkgolide C with the content of more than 80%, in which less than 5% of Ginkgolide A is present.
The method of the invention can obtain a high-purity Ginkgolide C with a purity of more than 97% by the separation and purification from the root bark of ginkgo. Moreover, the method of the invention has advantages such as the simple process flow, the good product quality and the low cost of industrial production and so on.
The invention will be further illustrated by the following examples.
(1) 800 L of 50% ethanol was added to 100 kg of root bark of ginkgo, and the resulting mixture was heated to 70° C. to extract for 2 hours;
(2) the extract was concentrated under vacuum to remove ethanol, and the concentration was conducted under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C. until no taste of ethanol was present, and the volume of the concentrate was about 200 L;
(3) the concentrate was separated by macroporous resin column chromatography, the type of the resin was AB-8, the amount of the resin was 100 kg, and the diameter-height ratio of the column was 1:8 or 1:10;
(4) after the concentrate was loaded on the column, the column was washed with 200 L of pure water to remove impurities, and then was eluted with 300 L to 400 L of 80% to 95% by weight of an ethanol solution;
(5) the eluate was concentrated under vacuum, and the concentration was conducted under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C., so as to obtain a reddish brown extractum;
(6) the reddish brown extractum was heated in water to boiling to form a solution, and then the solution was refrigerated at 2° C. to 6° C. over night;
(7) the supernatant solution was concentrated to ⅕ volume of the initial volume to produce a large number of lactone particles, and then filtered under vacuum with filter paper to obtain a white mixed crude crystal of Ginkgolides A, B and C;
(8) the crude crystal was dissolved in 95% by weight of ethanol to form a supersaturated solution, and then underwent fractional crystallization to remove Ginkgolides A and B;
(9) the mother liquor was further concentrated until a large number of crystals emerged, and then filtered under vacuum to obtain a crystal of Ginkgolide C with a content of more than 80%;
(10) the crystal was dissolved in 95% ethanol and recrystallized several times to obtain 110 g of a high-purity crystal of Ginkgolide C.
(1) 500 L of water was added to 50 kg of root bark of ginkgo, and the resulting mixture was extracted under the condition same as that of Example 1;
(2) the filtrate was loaded on macroporous resin column, and then separated via dynamic adsorption by D101 resin;
(3)-(9) were same as those of Example 1 to obtain 50 g of a crystal of Ginkgolide C with a purity of more than 97%.
Claims (9)
1. A method for separating and purifying Ginkgolide C from root bark of ginkgo, comprising the steps of:
(1) extracting the root bark of ginkgo as a raw material with 50% by weight of ethanol;
(2) concentrating the resulting extract under vacuum to remove ethanol;
(3) loading the resulting concentrate on a macroporous resin column chromatography;
(4) washing the column with 2 folds column volume of pure water to remove impurities, and then eluting the column with 80% to 95% by weight of an ethanol solution;
(5) concentrating the eluate under vacuum to dryness to obtain a yellow crude extract;
(6) heating the crude extract in water to boiling to form a solution, and then refrigerating the solution;
(7) obtaining a supernatant from the refrigerated solution and concentrating the supernatant to ⅕ volume of the initial volume to produce a large number of lactone particles, and then filtering under vacuum with filter paper to obtain a white mixed crude crystal of ginkgolides;
(8) dissolving the crude crystal in 95% by weight of ethanol to form a supersaturated solution, refrigerating and crystallizing the supersaturated solution to remove Ginkgolides A and B;
(9) concentrating and recrystallizing the resulting solution to obtain a crystal of Ginkgolide C with a content of more than 80%; and
(10) recrystallizing the crystal with ethanol several times to obtain a high-purity crystal of Ginkgolide C.
2. The method according to claim 1 , wherein in the step (1), 50% by weight of ethanol is added at a material-liquid ratio of 1:8, and the resulting mixture is heated to 70° C. to extract for 2 hours.
3. The method according to claim 1 , wherein in step (2), the extract is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C. until no taste of ethanol is present.
4. The method according to claim 1 , wherein in step (3), the type of the resin is DM130, D101 or AB-8.
5. The method according to claim 1 , wherein in step (4), the pure water for removing the impurities is neutral, the amount of the pure water is 2 folds column volume; and the amount of 80% to 95% by weight of ethanol for eluting is 3-4 folds column volume.
6. The method according to claim 1 , wherein in step (5), the eluate is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C. to 70° C.
7. The method according to claim 1 , wherein in the step (6), the solution is refrigerated at a temperature of 2° C. to 6° C. for 12 hours.
8. The method according to claim 1 , wherein in the step (7), the supernatant is concentrated under a vacuum degree of 0.08 MPa and a temperature of 60° C.
9. The method according to claim 1 , wherein in the step (10), the crystal is recrystallized three times.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201110006786 | 2011-03-21 | ||
CN20111006786.9 | 2011-03-21 | ||
CN 201110067186 CN102199159B (en) | 2011-03-21 | 2011-03-21 | Method for separating and purifying ginkgolide C in ginkgo root bark |
PCT/CN2012/071584 WO2012126308A1 (en) | 2011-03-21 | 2012-02-24 | Method for separating and purifying ginkgolide c from root and skin of ginkgo |
Publications (2)
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US20140039202A1 US20140039202A1 (en) | 2014-02-06 |
US8765196B2 true US8765196B2 (en) | 2014-07-01 |
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US14/006,474 Expired - Fee Related US8765196B2 (en) | 2011-03-21 | 2012-02-24 | Method for separating and purifying Ginkgolide C from root bark of ginkgo |
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US (1) | US8765196B2 (en) |
CN (1) | CN102199159B (en) |
WO (1) | WO2012126308A1 (en) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102199159B (en) * | 2011-03-21 | 2013-07-03 | 贵州大学 | Method for separating and purifying ginkgolide C in ginkgo root bark |
CN111747914B (en) * | 2019-03-29 | 2023-01-13 | 浙江康恩贝制药股份有限公司 | Compound separated from ginkgo root bark and application thereof |
CN113801133B (en) * | 2021-10-28 | 2022-08-19 | 江苏得乐康生物科技有限公司 | Preparation method of ginkgolide and monomer contained in ginkgolide |
CN114380776B (en) * | 2021-11-04 | 2023-05-23 | 中山大学 | Sesquiterpene electrophilic natural product, and separation preparation method and application thereof |
Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5541183A (en) * | 1993-12-31 | 1996-07-30 | Sunkyong Industries Co., Ltd. | Ginkgolide derivatives |
CN1195665A (en) | 1997-12-02 | 1998-10-14 | 周国柱 | Method for extracting ginkgo lactone and preparation containing the same |
US6174531B1 (en) * | 1997-11-25 | 2001-01-16 | Pharmanex Inc. | Methods of preparation of bioginkgo |
US20030031736A1 (en) * | 2001-07-11 | 2003-02-13 | The Trustees Of Columbia University In The City Of New York | Method for isolating terpene trilactones (ginkgolides, bilobalide) from leaves and pharmaceutical powders of ginkgo biloba |
US20030152654A1 (en) * | 1998-03-19 | 2003-08-14 | Xie De Long | Ginkgo biloba composition, method to prepare the same and uses thereof |
US20030225052A1 (en) * | 2002-03-29 | 2003-12-04 | Kristian Stromgaard | Analogs of terpene trilactones from Ginkgo biloba and related compounds and uses thereof |
US6693091B2 (en) * | 2002-03-29 | 2004-02-17 | The Trustees Of Columbia University In The City Of New York | Analogs of terpene trilactones from Ginkgo biloba for bioorganic and imaging studies |
CN1847237A (en) | 2006-04-13 | 2006-10-18 | 厦门国宇知识产权研究有限公司 | Ginkgo leaf extract and production process of separating high purity effective component of the extract |
US20080108837A1 (en) * | 2003-11-12 | 2008-05-08 | The Trustees Of Columbia University In The City Of New York | Separation Of Ginkgolides And Bilobalide From G. Biloba |
CN101412722A (en) | 2007-10-15 | 2009-04-22 | 桂林市振达生物科技有限责任公司 | Method for extracting and separating bilobalide C from ginkgo leaf |
US20090156668A1 (en) * | 2004-03-19 | 2009-06-18 | The Trustees Of Columbia University In The City Of New York | Ginkgolide Compounds, Compositions, And Extracts, And Uses Thereof |
CN101974014A (en) | 2010-09-27 | 2011-02-16 | 徐州技源天然保健品有限公司 | Manufacturing technology for extracting ginkalide A and C from root and bark of maidenhair tree |
CN102199159A (en) | 2011-03-21 | 2011-09-28 | 贵州大学 | Method for separating and purifying ginkgolide C in ginkgo root bark |
CN102464666A (en) * | 2010-11-09 | 2012-05-23 | 上海医药工业研究院 | Preparation method for ginkgolide C |
CN102627656A (en) * | 2012-04-19 | 2012-08-08 | 曹明成 | Process for extraction and separation of ginkgolides A, B, C, J, M and bilobalide |
-
2011
- 2011-03-21 CN CN 201110067186 patent/CN102199159B/en not_active Expired - Fee Related
-
2012
- 2012-02-24 WO PCT/CN2012/071584 patent/WO2012126308A1/en active Application Filing
- 2012-02-24 US US14/006,474 patent/US8765196B2/en not_active Expired - Fee Related
Patent Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5541183A (en) * | 1993-12-31 | 1996-07-30 | Sunkyong Industries Co., Ltd. | Ginkgolide derivatives |
US6174531B1 (en) * | 1997-11-25 | 2001-01-16 | Pharmanex Inc. | Methods of preparation of bioginkgo |
CN1195665A (en) | 1997-12-02 | 1998-10-14 | 周国柱 | Method for extracting ginkgo lactone and preparation containing the same |
US20030152654A1 (en) * | 1998-03-19 | 2003-08-14 | Xie De Long | Ginkgo biloba composition, method to prepare the same and uses thereof |
US20030031736A1 (en) * | 2001-07-11 | 2003-02-13 | The Trustees Of Columbia University In The City Of New York | Method for isolating terpene trilactones (ginkgolides, bilobalide) from leaves and pharmaceutical powders of ginkgo biloba |
US6693091B2 (en) * | 2002-03-29 | 2004-02-17 | The Trustees Of Columbia University In The City Of New York | Analogs of terpene trilactones from Ginkgo biloba for bioorganic and imaging studies |
US20030225052A1 (en) * | 2002-03-29 | 2003-12-04 | Kristian Stromgaard | Analogs of terpene trilactones from Ginkgo biloba and related compounds and uses thereof |
US20080108837A1 (en) * | 2003-11-12 | 2008-05-08 | The Trustees Of Columbia University In The City Of New York | Separation Of Ginkgolides And Bilobalide From G. Biloba |
US20090156668A1 (en) * | 2004-03-19 | 2009-06-18 | The Trustees Of Columbia University In The City Of New York | Ginkgolide Compounds, Compositions, And Extracts, And Uses Thereof |
CN1847237A (en) | 2006-04-13 | 2006-10-18 | 厦门国宇知识产权研究有限公司 | Ginkgo leaf extract and production process of separating high purity effective component of the extract |
CN101412722A (en) | 2007-10-15 | 2009-04-22 | 桂林市振达生物科技有限责任公司 | Method for extracting and separating bilobalide C from ginkgo leaf |
CN101974014A (en) | 2010-09-27 | 2011-02-16 | 徐州技源天然保健品有限公司 | Manufacturing technology for extracting ginkalide A and C from root and bark of maidenhair tree |
CN102464666A (en) * | 2010-11-09 | 2012-05-23 | 上海医药工业研究院 | Preparation method for ginkgolide C |
CN102199159A (en) | 2011-03-21 | 2011-09-28 | 贵州大学 | Method for separating and purifying ginkgolide C in ginkgo root bark |
CN102627656A (en) * | 2012-04-19 | 2012-08-08 | 曹明成 | Process for extraction and separation of ginkgolides A, B, C, J, M and bilobalide |
Non-Patent Citations (3)
Title |
---|
PCT/CN2012/071584 International Search Report mailed May 31, 2012, with English translation, 4 pages. |
PCT/CN2012/071584 Written Opinion mailed May 31, 2012, with English translation, 11 pages. |
PCTCN2012071584 International Search Report mailed May 31, 2012, and English Translation, 4 pages. |
Also Published As
Publication number | Publication date |
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CN102199159B (en) | 2013-07-03 |
WO2012126308A1 (en) | 2012-09-27 |
CN102199159A (en) | 2011-09-28 |
US20140039202A1 (en) | 2014-02-06 |
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